Radio-responsive recA promoter significantly increases TNFα production in recombinant clostridia after 2 Gy irradiation

Abstract

One of the major problems with gene therapy today is

Potential therapeutic applications of recombinant, invasive E. coli

“…34 Other types of bacteria are currently being developed as anticancer agents. [6][7][8][9][10]35 In these strategies, spores of anaerobic bacteria are injected and selectively grow within the necrotic regions of tumours where they find a niche to grow. For example, C. novyi has shown some dramatic antitumour effects in combination with conventional chemotherapeutic drugs 35 and Salmonella are capable of targeting, colonizing and eliciting growth suppression of tumours in mice.…”

“…More recently, this concept has been re-evaluated using attenuated strains of Salmonella 6,7 and Clostridium. [8][9][10] A genetically attenuated strain of Salmonella (VNP20009) 7 was recently used in a clinical trial. 11 VNP20009 demonstrated marked toxicity when injected above 3 Â 10 8 CFU/m 2 .…”

Can engineered bacteria help control cancer?

“…In this approach, targeting bacteria are engineered to produce enzymes that can activate prodrugs within the tumor (9,29). Another possibility is to place the genes of prodrug-activating enzymes under the control of radiationinducible promoters to provide spatial and temporal control, thus enabling selective killing of tumor cells while sparing normal cells (28,30). So what are the potential problems with bacteriolytic therapy?…”

“…crease the sensitivity of tumors to radiation therapy and͞or evoke a host immune response (28). Another approach is bacteria-directed enzyme prodrug therapy (BDEP T), a variation of antibodydirected enzyme prodrug therapy (ADEPT).…”

Quorum-sensing Salmonella selectively trigger protein expression within tumors

“…Precise triggering of expression can boost drug concentration within tumors while minimizing harmful side effects (6). Salmonella can be engineered to induce protein expression in response to molecular triggers, radiation, or hypoxia (6,11,(13)(14)(15)(16)(17)(18). Molecular triggers are limited because small molecules cannot diffuse deep into tissue (19)(20)(21).…”